Our ultimate aim is to attempt to perfect a vaccine containing purified and chemically defined enterobacterial common antigenic determinants which would give rise to antibodies for protecting against a variety of infections due to Enterobacteriaceae. The experimentation which we have performed to date with crude and partially purified antigens clearly indicates that protective activity does indeed exist (actively and passively) to cross reacting antigen(s) when tested in an experimental hematogenous and retrograde pyelonephritis model. Although inferences concerning the chemical nature and anatomical locus of common antigen within the cell have been drawn, considerable ambiguity exists deriving from both experimental, as well as inherent biological complexities of the system. No purified antigenic component has as yet been obtained which remains immunogenic. Therefore, all of the antisera available for investigative purposes were produced with crude, or so-called partially purified antigen preparations and are consequently not homogeneous. There is no way to assess the variability of different antisera prepared to these different antigenic preparations. We have focused attention on the use of a technique for disruption of cells under some of the mildest conditions available and separation of cell fractions by centrifugal procedures in the cold. Research presently in progress has placed particular emphasis on isolation of intact anatomical components which exhibit specific immunological properties. To date this has resulted in the observation of phenomena associated with the common antigenic response which are indeed different from what has previously been reported. Obtaining a purified and chemically defined common antigen which is immunogenic would allow us to define more precisely the role of common antigen(s) antibodies in protection. Furthermore, the relationship of these protective antibodies to other possible cross-reacting antigens, for example, Re glycolipid, could be evaluated. If the protective data can be further substantiated with purified and chemically defined common antigens, human trials may well be in order.